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The molecular chaperone Hsp90 provides a promising target because it supports survival, virulence, and drug resistance in a variety of pathogens. Herein, we report on the structural optimization and structure\u2013activity relationship studies of 3,4\u2010isoxazolediamide analogs. As a new class of fungal Hsp90 inhibitor, compound <jats:bold>B25<\/jats:bold> was found to have good synergistic effects with fluconazole and to avoid potential mammalian toxicity. It also showed remarkable metabolic stability in vitro. Collectively, <jats:bold>B25<\/jats:bold> could be a promising lead compound for drug discovery targeting fungal Hsp90 and deserves further investigation.<\/jats:p>","DOI":"10.1002\/ardp.202200266","type":"journal-article","created":{"date-parts":[[2022,8,27]],"date-time":"2022-08-27T13:14:12Z","timestamp":1661606052000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Design, synthesis, and evaluation of novel 3,4\u2010isoxazolediamide derivatives for the combination treatment of azole\u2010resistant candidiasis"],"prefix":"10.1002","volume":"355","author":[{"given":"Lei","family":"Liu","sequence":"first","affiliation":[{"name":"Key Laboratory of Structure\u2010Based Drug Design and Discovery, Ministry of Education, School of Pharmaceutical Engineering Shenyang Pharmaceutical University  Shenyang 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